Treatments for lupus nephritis: A systematic review and network metaanalysis

Objective. To compare benefits and harms of lupus nephritis (LN) induction and maintenance treatments. Methods. We performed a systematic review and Bayesian network metaanalyses of randomized controlled trials (RCT) of immunosuppressive drugs or corticosteroids (CS) in LN. OR and 95% credible intervals (CrI) were calculated. Results. There were 65 RCT that met inclusion and exclusion criteria. Significantly lower risk of endstage renal disease (ESRD; 17 studies) was seen with cyclophosphamide (CYC; OR 0.49, 95% CrI 0.25-0.92) or CYC + azathioprine (AZA; OR 0.18, 95% CrI 0.05-0.57) compared with standard-dose CS, and with high-dose (HD) CYC (OR 0.16, 95% CrI 0.03-0.61) or CYC + AZA (OR 0.10, 95% CrI 0.03-0.34) compared with HD CS. HD CS was associated with higher risk of ESRD compared with CYC (OR 3.59, 95% CrI 1.30-9.86), AZA (OR 2.93, 95% CrI 1.08-8.10), or mycophenolate mofetil (MMF; OR 7.05, 95% CrI 1.66-31.91). Compared with CS, a significantly higher proportion of patients had renal response (14 studies) when treated with CYC (OR 1.98, 95% CrI 1.13-3.52), MMF (OR 2.42, 95% CrI 1.27-4.74), or tacrolimus (TAC; OR 4.20, 95% CrI 1.29-13.68). No differences were noted for the risk of malignancy (15 studies). The risk of herpes zoster (17 studies) was as follows: OR (95% CrI) MMF versus CS 4.38 (1.02-23.87), CYC versus CS 6.64 (1.97-25.71), TAC versus CS 9.11 (1.13-70.99), and CYC + AZA versus CS 8.46 (1.99-43.61). Conclusion. Renal benefits and the risk of herpes zoster were higher for immunosuppressive drugs versus CS. Data on relative and absolute differences are now available, which can be incorporated into patient-physician discussions related to systemic lupus erythematosus medication use.